The FDA has granted approval to cemiplimab-rwlc, for the first-line treatment of patients with advanced non-small cell lung cancer whose tumors have high PD-L1 expression, as determined by an FDA-approved test. Patients must either have metastatic or locally advanced tumors that are not candidates for surgical resection or definitive chemoradiation, and the tumors must not have EGFR, ALK, or ROS1 aberrations.
The FDA has granted approval to cemiplimab-rwlc (Libtayo), for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (tumor proportion score ≥50%), as determined by an FDA-approved test. Patients must either have metastatic or locally advanced tumors that are not candidates for surgical resection or definitive chemoradiation, and the tumors must not have EGFR, ALK, or ROS1 aberrations.1
The announcement of the new indication for cemiplimab was made in a press release from Regeneron and Sanofi. The approval is 7 days ahead of the Prescription Drug User Fee Act target action date, which was set after the drug received Priority Review designation based on positive results from the phase 3 EMPOWER-Lung1 trial (NCT03088540).
"The approval of Libtayo to treat first-line advanced non-small cell lung cancer with high PD-L1 expression means physicians and patients have a potent new treatment option against this deadly disease," said Naiyer Rizvi, MD, Price Family Professor of Medicine, director of Thoracic Oncology and co-director of Cancer Immunotherapy at Columbia University Irving Medical Center.
"Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases, or who had locally advanced disease and were not candidates for definitive chemoradiation. This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice,” added Rizvi, whose is also a steering committee member of the trial."
EMPOWER-Lung1 is an open-label, randomized, multicenter trial. In the study, the intent-to-treat population included 710 patients. Of those included, 88 patients were identified as having a PD-L1 expression of ≥ 50%, as identified by the PD-L1 IHC 22C3 pharmDx kit. The coprimary end points of the study were overall survival (OS) and progression-free survival (PFS). The secondary end points assessed were objective response rate (ORR), duration of response (DOR), health-related quality of life (HRQoL), and safety.
Patients in the ITT population achieved a 22.1-month OS (95% CI, 17.7 to not evaluable [NE]) with cemiplimab compared with 14.3 months (95% CI, 11.7-19.2) in the chemotherapy arm (HR, 0.68; 95% CI, 0.53-0.87; P = .0022). The median PFS was 6.2 months (95% CI, 4.5-8.3) with cemiplimab compared with 5.6 months (95% CI, 4.5-6.1) with chemotherapy (HR, 0.59; 95% CI, 0.49-0.72; P = .0001).
In the PD-L1-high population, the median OS was not reached with cemiplimab (95% CI, 17.9-NE) compared with 14.2 months (95% CI, 11.2-17.5) in the chemotherapy arm (HR, 0.57; 95% CI, 0.42-0.77; P = .0002). The median PFS in the high PD-L1 expression group was 8.2 months (95% CI, 6.1-8.8) with cemiplimab compared with 5.7 months (95% CI, 4.5-6.2) in the chemotherapy arm (HR, 0.53; 95% CI, 0.43-0.68; P = .0001).
The benefits in terms of OS and PFS in the cemiplimab arm were seen across the subgroup populations assessed in the study.
Data presented virtual during the 2020 European Society of Medical Oncology (ESMO) Annual Congress also showed that responses were superior in the cemiplimab arm compared with the chemotherapy arm. In the ITT population, the ORR achieved was 6.5% (95% CI, 31.5%-41.8%) with cemiplimab compared with only 20.6% (95% CI, 16.5%-25.2%) with chemotherapy (P < .0001). Among the high PD-L1 patients, cemiplimab led to an ORR of 39.2% (95% CI, 33.5%-45.2%) with cemiplimab versus 20.4% (95% CI, 15.8%-25.6%) with chemotherapy (P < .0001).2
The safety analysis of EMPOWER-Lung1 supported the positive benefit-risk profile of cemiplimab, according to the ESMO Meeting data.
Treatment-emergent adverse events (TEAEs) were observed in 88.2% of patient in the study with 37.2% being grade 3 to 5 in severity. TEAEs led to treatment discontinuation in 6.5% of the population and death in 9.6%. Immune-related AEs were seen in 17.5% of patients and lead to discontinuation in 2.5% of patients. Immune-related AEs also led to death in 0.3%.
The most common TEAEs of any-grade observed in the study were anemia (14.6%), decreased appetite (11.8%), fatigue (10.1%), pneumonia (9.3%), and constipation (7.6%).
"With this third approval for Libtayo, we are proud to deliver on our ambition to bring our PD-1 inhibitor to patients in need with difficult-to-treat cancers, such as advanced non-small cell lung cancer," said Peter C. Adamson, MD, Global Development head, Oncology and Pediatric Innovation at Sanofi. "As the leading cause of cancer deaths globally, the need for additional therapeutic options in advanced NSCLC is clear. Libtayo allows physicians to further optimize treatment of these patients whose tumors have high expression of PD-L1.”
1. FDA approves Libtayo® (cemiplimab-rwlc) monotherapy for patients with first-line advanced non-small cell lung cancer with PD-L1 expression of ≥50%. News release. Regeron and Sanofi. February 22, 2021. Accessed February 22, 2021. https://bit.ly/2ZHfo9Y
2. Sezer A, Kilickap S, Gumus M, et al. EMPOWER-Lung 1: Phase 3 first-line (1L) cemiplimab monotherapy vs platinum-doublet chemotherapy (Chemo) in advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. 2020 European Society for Medical Oncology Virtual Congress; September 19-21, 2020. Abstract LBA52.